| First Author | Yan W | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 490 |
| Issue | 2 | Pages | 84-90 |
| PubMed ID | 28478040 | Mgi Jnum | J:251050 |
| Mgi Id | MGI:6103791 | Doi | 10.1016/j.bbrc.2017.05.011 |
| Citation | Yan W, et al. (2017) Knockout of immunoproteasome subunit beta2i ameliorates cardiac fibrosis and inflammation in DOCA/Salt hypertensive mice. Biochem Biophys Res Commun 490(2):84-90 |
| abstractText | The immunoproteasome is a multicatalytic protease complex in all eukaryotic cells, which plays a key role in regulating essential cellular processes. However, the role of immunoproteasome subunit beta2i in regulation of cardiac fibrosis and inflammation in deoxycorticosterone-acetate (DOCA)/salt mice remains unknown. Wild-type (WT) and beta2i knockout (KO) mice were subjected to uninephrectomy and DOCA/salt treatment for 21 days. Blood pressure was measured by the tail-cuff system. Cardiac function and remodeling were examined by echocardiography, hematoxylin-eosin (H&E) and Masson''s trichrome staining. The gene and protein expressions were detected by quantitative real-time PCR, and Western blot analysis. After 21 days, DOCA/salt treatment significantly up-regulated the expression of beta2i mRNA and protein in the hearts. Moreover, systolic blood pressure and heart weight/body weight (HW/BW) ratio were significantly higher in DOCA/salt mice than in sham groups, and these effects were markedly reversed in beta2i knockout mice. Importantly, DOCA/salt-induced cardiac fibrosis, inflammation and the expression of collagen I, collagen III, alpha-SMA, IL-1beta, IL-6 and TNF-alpha in the wild-type hearts, which were markedly attenuated by beta2i knockout. These beneficial effects were due, at least in part, to the inhibition of IkappaBalpha/NF-kappaB and TGF-beta1/Smad2/3 signaling pathways. Collectively, these findings indicate that knockout of beta2i ameliorates DOCA/salt-induced cardiac fibrosis and inflammation, and may be a novel potential therapeutic target for hypertensive heart diseases. |
